NNC-45-0095
Chemical Name: 1-Ethyl-2-(4-hydroxyphenyl)pyrrolo[2,1,5-cd]indolizine; 4-(1-Ethylpyrrolo[2,1,5-cd]indolizin-2-yl)phenol
CAS No. 217318-90-6
项目整合开发状态: Preclinical
项目研究机构: Novo Nordisk (Originator)
合成路线:The title compound has been prepared by two related procedures.Alkylation of 2-propylpyridine (I) with 4-methoxyphenacyl bromide (II) in refluxing acetone gave the pyridinum salt (III),which was further cyclized to the indolizine (IV) using aqueous NaHCO3.Condensation of (IV) with dimethyl acetylenedicarboxylate (V),followed by oxidation with 2,3-dichloro-5,6-dicyanoquinone furnished the tricyclic system (VI).Hydrolysis of the diester of (VI) and subsequent decarboxylation of the resulting diacid (VII) produced the methoxy derivative (VIII).Finally,demethylation of (VIII) using AlCl3 and ethanethiol gave rise to the title phenol compound.
📌 参考资料/链接：
参考文献标题:Pyrrolo[2,1,5-cd]indolizine derivs.useful in the prevention or treatment of estrogen related diseases or syndromes
文献作者:Christiansen,L.B.; Kanstrup,A.; Jacobsen,P.; Jorgensen,A.S.; Bury,P.S.(Novo Nordisk A/S)
参考来源:EP 0986560; US 6075036; WO 9855482
📄 详细内容
合成路线:In a very close procedure,alkylation of 2-propylpyridine (I) was effected with 4-benzyloxyphenacyl bromide (IX).The resulting pyridinium salt (X) was cyclized with NaHCO3 to give (XI),which was then condensed with dimethyl acetylenedicarboxylate (V) as before to give the tricyclic system (XII).Hydrolysis of diester (XII) to diacid (XIII),followed by decarboxylation with copper in hot quinoline yielded (XIV).The benzyl protecting group of (XIV) was then removed by catalytic hydrogenolysis in the presence of Pd/C.
参考文献标题:Synthesis and pharmacology of a novel pyrrolo[2,1,5-cd] indolizine (NNC 45-0095),a high affinity non-steroidal agonist for the estrogen receptor
文献作者:Jorgensen,A.S.; Jacobsen,P.; Christiansen,L.B.; Bury,P.S.; Kanstrup,A.; Thorpe,S.M.; Bain,S.; Naerum,L.; Wassermann,K.
参考来源:Bioorg Med Chem Lett 2000,10(4),399
产品链接: CAS No. 217318-90-6››